CCKA and CCKB receptor subtypes both mediate the effects of CCK-8 on myenteric neurons in the guinea-pig ileum.
The effects of cholecystokinin (CCK-8) on myenteric S neurons were investigated by intracellular recording techniques, with the aim to determine the CCK receptor subtypes involved. CCK-8 (1-1000 nM) evoked concentration-dependent long-lasting excitatory responses in 45 of 54 neurons. CCK receptor antagonists were applied to 15 neurons in which CCK-8 evoked an excitatory response. In 5 of these neurons, application of the CCKA antagonist L-364,718 (100-500 nM) antagonized the action of CCK-8 and the CCKB antagonist L-365,260 (500 nM) had no effect. L-365,260 (100-500 nM) antagonized the CCK-8 induced response in 5 neurons, on which L-364,718 had no effect. In the other 5 neurons each antagonist (500 nM) partly inhibited the CCK-8 evoked excitation and application of both antagonists (500 nM) caused a complete blockade of the response to CCK-8. The selective CCKB receptor agonist CCK-8NS had similar excitatory effects as CCK-8, but only on the neurons in which CCK-8 evoked effects were antagonized by L-365,260. The results demonstrate that the excitatory effects of CCK-8 are mediated by both CCKA and CCKB receptor subtypes. Further, the results indicate that some neurons possess exclusively the CCKA or the CCKB receptor subtype, but others possess both subtypes.
Schutte
I W
IW
Department of Human and Animal Physiology, Agricultural University, Wageningen, The Netherlands.
Akkermans
L M
LM
Kroese
A B
AB
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D020109:Devazepide; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D006727:Hormone Antagonists / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000294:innervation*; D066298:In Vitro Techniques; D009197:Myenteric Plexus / Q000166:cytology* / Q000187:drug effects*; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012844:Sincalide / Q000494:pharmacology*
D001570:Benzodiazepinones; D006727:Hormone Antagonists; D010671:Phenylurea Compounds; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C058121:L 365260; D020109:Devazepide; D012844:Sincalide